A system to detect mutations at the HGPRT locus in cultured, diploid human fibroblasts has been established in this laboratory. The carcinogen N-acetoxy-2-acetylaminofluorene has been studied and found to be mutagenic in human cells. Dose response in the induced mutation frequency was demonstrated. As judged by enzyme assays, most of the cells which grow in selective medium are true mutants. Because of the relevance of the cultured diploid human fibroblast and because so much is known about the biochemistry and genetics of the HGPRT locus (HGPRT= hypoxanthine guanine phosphoribosyl transferase), this mutation detection system is potentially useful for environmental monitoring.